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Parkinson Disease: HELP
Articles from Emory University
Based on 165 articles published since 2008
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These are the 165 published articles about Parkinson Disease that originated from Emory University during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
1 Editorial Parkinson Disease Risk in Patients With Rosacea. 2016

Wingo, Thomas S. ·Department of Neurology, Emory University, Atlanta, Georgia2Department of Human Genetics, Emory University, Atlanta, Georgia3Division of Neurology, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia. ·JAMA Neurol · Pubmed #26998584.

ABSTRACT: -- No abstract --

2 Editorial VMAT2 and Parkinson's disease: harnessing the dopamine vesicle. 2014

Lohr, Kelly M / Miller, Gary W. ·Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA, 30322, USA. ·Expert Rev Neurother · Pubmed #25220836.

ABSTRACT: Despite a movement away from dopamine-focused Parkinson's disease (PD) research, a recent surge of evidence now suggests that altered vesicular storage of dopamine may contribute to the demise of the nigral neurons in this disease. Human studies demonstrate that the vesicular monoamine transporter 2 (VMAT2; SLC18A2) is dysfunctional in PD brain. Moreover, studies with transgenic mice suggest that there is an untapped reserve capacity of the dopamine vesicle that could be unbridled by increasing VMAT2 function. Therapeutic manipulation of VMAT2 level or function has the potential to improve efficacy of dopamine derived from administered levodopa, increase dopamine neurotransmission from remaining midbrain dopamine neurons and protect against neurotoxic insults. Thus, the development of drugs to enhance the storage of release of dopamine may be a fruitful avenue of research for PD.

3 Editorial Sex differences in neurological and psychiatric disorders. 2014

Young, Larry J / Pfaff, Donald W. ·Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, United States. Electronic address: lyoun03@emory.edu. · Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021, United States. ·Front Neuroendocrinol · Pubmed #24882637.

ABSTRACT: -- No abstract --

4 Review The Promise of Telemedicine for Movement Disorders: an Interdisciplinary Approach. 2018

Ben-Pazi, H / Browne, P / Chan, P / Cubo, E / Guttman, M / Hassan, A / Hatcher-Martin, J / Mari, Z / Moukheiber, E / Okubadejo, N U / Shalash, A / Anonymous1401121. ·Neuropediatric unit, Shaare Zedek Medical Center, Jerusalem, Israel. · Neurology Department, University Hospital Galway, Newcastle Road, Galway, Ireland. · School of Medicine, National University of Ireland Galway, Galway, Ireland. · Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital of Capital Medical University Beijing, Beijing, China. · Neurology Department, University Hospital, Burgos, Spain. mcubo@saludcastillayleon.es. · University of Toronto, Toronto, ON, Canada. · Department of Neurology, Mayo Clinic, Rochester, MN, USA. · Movement Disorders Program, Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. · Parkinson's Disease and Movement Disorders Program, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, USA. · Department of Neurology, Johns Hopkins Medicine, Baltimore, MD, USA. · Neurology Unit, Department of Medicine, College of Medicine, University of Lagos, Lagos State, Nigeria. · Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. ·Curr Neurol Neurosci Rep · Pubmed #29654523.

ABSTRACT: PURPOSE OF REVIEW: Advances in technology have expanded telemedicine opportunities covering medical practice, research, and education. This is of particular importance in movement disorders (MDs), where the combination of disease progression, mobility limitations, and the sparse distribution of MD specialists increase the difficulty to access. In this review, we discuss the prospects, challenges, and strategies for telemedicine in MDs. RECENT FINDINGS: Telemedicine for MDs has been mainly evaluated in Parkinson's disease (PD) and compared to in-office care is cost-effective with similar clinical care, despite the barriers to engagement. However, particular groups including pediatric patients, rare MDs, and the use of telemedicine in underserved areas need further research. Interdisciplinary telemedicine and tele-education for MDs are feasible, provide similar care, and reduce travel costs and travel time compared to in-person visits. These benefits have been mainly demonstrated for PD but serve as a model for further validation in other movement disorders.

5 Review Metabotropic glutamate receptors: targets for neuroprotective therapies in Parkinson disease. 2018

Masilamoni, Gunasingh J / Smith, Yoland. ·Yerkes National Primate Research Center, Emory University, 954, Gatewood Rd NE, Atlanta, GA 30322, USA; Udall Center of Excellence for Parkinson's Disease, Emory University, 954, Gatewood Rd NE, Atlanta, GA 30322, USA. · Yerkes National Primate Research Center, Emory University, 954, Gatewood Rd NE, Atlanta, GA 30322, USA; Department of Neurology, Emory University, 954, Gatewood Rd NE, Atlanta, GA 30322, USA; Udall Center of Excellence for Parkinson's Disease, Emory University, 954, Gatewood Rd NE, Atlanta, GA 30322, USA. Electronic address: ysmit01@emory.edu. ·Curr Opin Pharmacol · Pubmed #29605730.

ABSTRACT: Metabotropic glutamate receptors (mGluRs) are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release and long term synaptic plasticity. Therefore, targeting specific mGluR subtypes by means of selective drugs could be a possible strategy for restoring normal synaptic function and neuronal activity of the BG in Parkinson disease (PD). Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of PD. Although the underlying mechanisms of these effects must be further studied, there is evidence that intracellular calcium regulation, anti-inflammatory effects, and glutamatergic network modulation contribute to some of these neuroprotective properties. It is noteworthy that these protective effects extend beyond midbrain dopaminergic neurons to include other monoaminergic cell groups for some mGluRs. In this review, we discuss evidence for mGluR-mediated neuroprotection in PD and highlight the challenges to translate these findings into human trials.

6 Review Long Road to Ruin: Noradrenergic Dysfunction in Neurodegenerative Disease. 2018

Weinshenker, David. ·Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: dweinsh@emory.edu. ·Trends Neurosci · Pubmed #29475564.

ABSTRACT: It has been known for decades that degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs in both Alzheimer's disease (AD) and Parkinson's disease (PD), but it was given scant attention. It is now recognized that hyperphosphorylated tau in the LC is the first detectable AD-like neuropathology in the human brain, α-synuclein inclusions in the LC represent an early step in PD, and experimental LC lesions exacerbate neuropathology and cognitive/behavioral deficits in animal models. The purpose of this review is to consider the causes and consequences of LC pathology, dysfunction, and degeneration, as well as their implications for early detection and treatment.

7 Review Monoamine Oxidases. 2018

Edmondson, Dale E / Binda, Claudia. ·Department of Biochemistry, Emory University, Atlanta, GA, USA. · Department of Biology and Biotechnology, University of Pavia, Pavia, Italy. claudia.binda@unipv.it. ·Subcell Biochem · Pubmed #29464559.

ABSTRACT: Monoamine oxidases A and B (MAO A and B) are mammalian flavoenzymes bound to the outer mitochondrial membrane. They were discovered almost a century ago and they have been the subject of many biochemical, structural and pharmacological investigations due to their central role in neurotransmitter metabolism. Currently, the treatment of Parkinson's disease involves the use of selective MAO B inhibitors such as rasagiline and safinamide. MAO inhibition was shown to exert a general neuroprotective effect as a result of the reduction of oxidative stress produced by these enzymes, which seems to be relevant also in non-neuronal contexts. MAOs were successfully expressed as recombinant proteins in Pichia pastoris, which allowed a thorough biochemical and structural characterization. These enzymes are characterized by a globular water-soluble main body that is anchored to the mitochondrial membrane through a C-terminal α-helix, similar to other bitopic membrane proteins. In both MAO A and MAO B the enzyme active site consists of a hydrophobic cavity lined by residues that are conserved in the two isozymes, except for few details that determine substrate and inhibitor specificity. In particular, human MAO B features a dual-cavity active site whose conformation depends on the size of the bound ligand. This article provides a comprehensive and historical review of MAOs and the state-of-the-art of these enzymes as membrane drug targets.

8 Review Pathophysiologic Basis of Movement Disorders. 2018

Wichmann, Thomas. ·Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA. ·Prog Neurol Surg · Pubmed #29332070.

ABSTRACT: Movement disorders are common and functionally disabling neurologic diseases. Studies over the last decades have investigated the pathophysiology of these diseases in considerable detail, leading to significant insights into their generation of motor disability. While genetically and clinically heterogeneous, most of them are accompanied by prominent and characteristic changes in firing rates and patterns in the basal ganglia, thalamus, and cortex. In recent years, researchers have placed increasing emphasis on the importance of oscillatory changes in firing in these structures, and have discovered that brain areas that were previously considered to be remote from the basal ganglia (such as the cerebellum and the pedunculopontine nucleus) are also highly significant in these disorders. The evolving pathophysiologic concepts have important implications for improving our understanding of the biology of these disorders, and for the development of more effective pharmacologic and surgical therapies with fewer side effects than seen with the currently available treatments. In this chapter, the known pathophysiology of three common movement disorders, Parkinson's disease, dystonia, and essential tremor, is reviewed.

9 Review Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. 2017

Obeso, J A / Stamelou, M / Goetz, C G / Poewe, W / Lang, A E / Weintraub, D / Burn, D / Halliday, G M / Bezard, E / Przedborski, S / Lehericy, S / Brooks, D J / Rothwell, J C / Hallett, M / DeLong, M R / Marras, C / Tanner, C M / Ross, G W / Langston, J W / Klein, C / Bonifati, V / Jankovic, J / Lozano, A M / Deuschl, G / Bergman, H / Tolosa, E / Rodriguez-Violante, M / Fahn, S / Postuma, R B / Berg, D / Marek, K / Standaert, D G / Surmeier, D J / Olanow, C W / Kordower, J H / Calabresi, P / Schapira, A H V / Stoessl, A J. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles, Madrid, Spain. · Universidad CEU San Pablo, Madrid, Spain. · CIBERNED, Madrid, Spain. · Department of Neurology, Philipps University, Marburg, Germany. · Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital and Attikon Hospital, University of Athens, Athens, Greece. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · Department of Medicine, University of Toronto, Toronto, Canada. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Corporal Michael J. Crescenz Veteran's Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Medical Sciences, Newcastle University, Newcastle, UK. · Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, Australia. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · China Academy of Medical Sciences, Institute of Lab Animal Sciences, Beijing, China. · Departments of Neurology, Pathology, and Cell Biology, the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA. · Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA. · Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Clinical Sciences Department, Newcastle University, Newcastle, UK. · Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark. · Human Neurophysiology, Sobell Department, UCL Institute of Neurology, London, UK. · Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Movement Disorders and Neuromodulation Center, Department of Neurology, University of California-San Francisco, San Francisco, California, USA. · Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA. · Parkinson's Institute, Sunnyvale, California, USA. · Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Department of Neurology, Universitätsklinikum Schleswig-Holstein, Christian Albrechts University Kiel, Kiel, Germany. · Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem, Israel. · Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel. · Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Medicine, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Barcelona, Spain. · Movement Disorders Clinic, Clinical Neurodegenerative Research Unit, Mexico City, Mexico. · Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. · Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Graduate Program, Rush University Medical Center, Chicago, Illinois, USA. · Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy. · University Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, UK. · Pacific Parkinson's Research Centre, Division of Neurology & Djavadf Mowafaghian Centre for Brain Health, University of British Columbia, British Columbia, Canada. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #28887905.

ABSTRACT: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

10 Review The role of neurotransmitters in the development of Parkinson's disease-related psychosis. 2017

Factor, S A / McDonald, W M / Goldstein, F C. ·Department of Neurology, Emory University School of Medicine, Atlanta, GA. · Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA. ·Eur J Neurol · Pubmed #28758318.

ABSTRACT: Psychotic symptoms are common, disabling non-motor features of Parkinson's disease (PD). Despite noted heterogeneity in clinical features, natural history and therapy response, current dogma posits that psychosis generally progresses in a stereotypic manner through a cascade of events that begins with minor hallucinations and evolves to severe hallucinations and delusions. Further, the occurrence of psychotic symptoms is believed to indicate a poor prognosis. Here we propose a classification scheme that outlines the pathogenesis of psychosis as it relates to dysfunction of several neurotransmitter systems. We hypothesize that several subtypes exist, and that PD psychosis is not consistently indicative of a progressive cascade and poor prognosis. The literature was reviewed from 1990 to 2017. An overview of the features of PD psychosis is followed by a review of data indicating the existence of neurotransmitter-related subtypes of psychosis. We found that ample evidence exists to demonstrate the presence of multiple subtypes of PD psychosis, which are traced to dysfunction of the following neurotransmitter systems: dopamine, serotonin and acetylcholine. Dysfunction of each of these systems is recognizable through their clinical features and correlates, and the varied long-term prognoses. Identifying which neurotransmitter system is dysfunctional may help to develop targeted therapies. PD psychosis has various subtypes that differ in clinical features, underlying pathology and pathophysiology, treatment response and prognosis. A novel classification scheme is presented that describes the clinical subtypes with different outcomes, which could lead to the development of targeted therapies. Future research should focus on testing the viability of this classification.

11 Review Microglial phenotypes in Parkinson's disease and animal models of the disease. 2017

Joers, Valerie / Tansey, Malú G / Mulas, Giovanna / Carta, Anna R. ·Department of Physiology, Emory University, Atlanta, GA, United States; Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States. · Department of Physiology, Emory University, Atlanta, GA, United States. Electronic address: malu.tansey@emory.edu. · Department of Biomedical Sciences, University of Cagliari, Italy. · Department of Biomedical Sciences, University of Cagliari, Italy. Electronic address: acarta@unica.it. ·Prog Neurobiol · Pubmed #27107797.

ABSTRACT: Over the last decade the important concept has emerged that microglia, similar to other tissue macrophages, assume different phenotypes and serve several effector functions, generating the theory that activated microglia can be organized by their pro-inflammatory or anti-inflammatory and repairing functions. Importantly, microglia exist in a heterogenous population and their phenotypes are not permanently polarized into two categories; they exist along a continuum where they acquire different profiles based on their local environment. In Parkinson's disease (PD), neuroinflammation and microglia activation are considered neuropathological hallmarks, however their precise role in relation to disease progression is not clear, yet represent a critical challenge in the search of disease-modifying strategies. This review will critically address current knowledge on the activation states of microglia as well as microglial phenotypes found in PD and in animal models of PD, focusing on the expression of surface molecules as well as pro-inflammatory and anti-inflammatory cytokine production during the disease process. While human studies have reported an elevation of both pro- or anti-inflammatory markers in the serum and CSF of PD patients, animal models have provided insights on dynamic changes of microglia phenotypes in relation to disease progression especially prior to the development of motor deficits. We also review recent evidence of malfunction at multiple steps of NFκB signaling that may have a causal interrelationship with pathological microglia activation in animal models of PD. Finally, we discuss the immune-modifying strategies that have been explored regarding mechanisms of chronic microglial activation.

12 Review Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease. 2015

DeLong, Mahlon R / Wichmann, Thomas. ·Department of Neurology, School of Medicine, Emory University, Atlanta, Georgia. · Department of Neurology, School of Medicine, Emory University, Atlanta, Georgia2Yerkes National Primate Research Center, Emory University, Atlanta, Georgia. ·JAMA Neurol · Pubmed #26409114.

ABSTRACT: IMPORTANCE: The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. OBJECTIVE: To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. EVIDENCE REVIEW: A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. FINDINGS: The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. CONCLUSIONS AND RELEVANCE: Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with drugs.

13 Review Cholinergic interneurons in the dorsal and ventral striatum: anatomical and functional considerations in normal and diseased conditions. 2015

Gonzales, Kalynda K / Smith, Yoland. ·Yerkes National Primate Research Center, Department of Neurology and Udall Center of Excellence for Parkinson's Disease Research, Emory University, Atlanta, Georgia. · Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York. ·Ann N Y Acad Sci · Pubmed #25876458.

ABSTRACT: Striatal cholinergic interneurons (ChIs) are central for the processing and reinforcement of reward-related behaviors that are negatively affected in states of altered dopamine transmission, such as in Parkinson's disease or drug addiction. Nevertheless, the development of therapeutic interventions directed at ChIs has been hampered by our limited knowledge of the diverse anatomical and functional characteristics of these neurons in the dorsal and ventral striatum, combined with the lack of pharmacological tools to modulate specific cholinergic receptor subtypes. This review highlights some of the key morphological, synaptic, and functional differences between ChIs of different striatal regions and across species. It also provides an overview of our current knowledge of the cellular localization and function of cholinergic receptor subtypes. The future use of high-resolution anatomical and functional tools to study the synaptic microcircuitry of brain networks, along with the development of specific cholinergic receptor drugs, should help further elucidate the role of striatal ChIs and permit efficient targeting of cholinergic systems in various brain disorders, including Parkinson's disease and addiction.

14 Review Therapeutic potential of berberine against neurodegenerative diseases. 2015

Jiang, WenXiao / Li, ShiHua / Li, XiaoJiang. ·Department of Microbiology and Molecular Genetics, Emory University, Atlanta, GA, 30322, USA. ·Sci China Life Sci · Pubmed #25749423.

ABSTRACT: Berberine (BBR) is an organic small molecule isolated from various plants that have been used in traditional Chinese medicine. Isolation of this compound was its induction into modern medicine, and its usefulness became quickly apparent as seen in its ability to combat bacterial diarrhea, type 2 diabetes, hypercholesterolemia, inflammation, heart diseases, and more. However, BBR's effects on neurodegenerative diseases remained relatively unexplored until its ability to stunt Alzheimer's disease (AD) progression was characterized. In this review, we will delve into the multi-faceted defensive capabilities and bio-molecular pathways of BBR against AD, Parkinson's disease (PD), and trauma-induced neurodegeneration. The multiple effects of BBR, some of which enhance neuro-protective factors/pathways and others counteract targets that induce neurodegeneration, suggest that there are many more branches to the diverse capabilities of BBR that have yet to be uncovered. The promising results seen provide a convincing and substantial basis to support further scientific exploration and development of the therapeutic potential of BBR against neurodegenerative diseases.

15 Review Causes and consequences of degeneration of the dorsal motor nucleus of the vagus nerve in Parkinson's disease. 2014

Greene, James G. ·Department of Neurology, Emory University , Atlanta, Georgia . ·Antioxid Redox Signal · Pubmed #24597973.

ABSTRACT: SIGNIFICANCE: Parkinson's disease (PD) is no longer considered merely a movement disorder caused by degeneration of dopamine neurons in the midbrain. It is now recognized as a widespread neuropathological syndrome accompanied by a variety of motor and nonmotor clinical symptoms. As such, any hypothesis concerning PD pathogenesis and pathophysiology must account for the entire spectrum of disease and not solely focus on the dopamine system. RECENT ADVANCES: Based on its anatomy and the intrinsic properties of its neurons, the dorsal motor nucleus of the vagus nerve (DMV) is uniquely vulnerable to damage from PD. Fibers in the vagus nerve course throughout the gastrointestinal (GI) tract to and from the brainstem forming a close link between the peripheral and central nervous systems and a point of proximal contact between the environment and areas where PD pathology is believed to start. In addition, DMV neurons are under high levels of oxidative stress due to their high level of α-synuclein expression, fragile axons, and specific neuronal physiology. Moreover, several consequences of DMV damage, namely, GI dysfunction and unrestrained inflammation, may propagate a vicious cycle of injury affecting vulnerable brain regions. CRITICAL ISSUES: Current evidence to suggest the vagal system plays a pivotal role in PD pathogenesis is circumstantial, but given the current state of the field, the time is ripe to obtain direct experimental evidence to better delineate it. FUTURE DIRECTIONS: Better understanding of the DMV and vagus nerve may provide insight into PD pathogenesis and a neural highway with direct brain access that could be harnessed for novel therapeutic interventions.

16 Review Treatment of the sleep disorders associated with Parkinson's disease. 2014

Trotti, Lynn Marie / Bliwise, Donald L. ·Department of Neurology, Emory University School of Medicine, 1841 Clifton Road NE, Atlanta, GA, 30329, USA, Lbecke2@emory.edu. ·Neurotherapeutics · Pubmed #24272458.

ABSTRACT: Sleep disorders are common in patients with Parkinson's disease (PD), and preliminary work has suggested viable treatment options for many of these disorders. For rapid eye movement sleep behavior disorder, melatonin and clonazepam are most commonly used, while rivastigmine might be a useful option in patients whose behaviors are refractory to the former. Optimal treatments for insomnia in PD have yet to be determined, but preliminary evidence suggests that cognitive-behavioral therapy, light therapy, eszopiclone, donepezil, and melatonin might be beneficial. Use of the wake-promoting agent modafinil results in significant improvement in subjective measures of excessive daytime sleepiness, but not of fatigue. Optimal treatment of restless legs syndrome and obstructive sleep apnea in PD are not yet established, although a trial of continuous positive airway pressure for sleep apnea was recently completed in PD patients. In those patients with early morning motor dysfunction and disrupted sleep, the rotigotine patch provides significant benefit.

17 Review The role of innate and adaptive immunity in Parkinson's disease. 2013

Kannarkat, George T / Boss, Jeremy M / Tansey, Malú G. ·Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA. ·J Parkinsons Dis · Pubmed #24275605.

ABSTRACT: In recent years, inflammation has become implicated as a major pathogenic factor in the onset and progression of Parkinson's disease. Understanding the precise role for inflammation in PD will likely lead to understanding of how sporadic disease arises. In vivo evidence for inflammation in PD includes microglial activation, increased expression of inflammatory genes in the periphery and in the central nervous system (CNS), infiltration of peripheral immune cells into the CNS, and altered composition and phenotype of peripheral immune cells. These findings are recapitulated in various animal models of PD and are reviewed herein. Furthermore, we examine the potential relevance of PD-linked genetic mutations to altered immune function and the extent to which environmental exposures that recapitulate these phenotypes, which may lead to sporadic PD through similar mechanisms. Given the implications of immune system involvement on disease progression, we conclude by reviewing the evidence supporting the potential efficacy of immunomodulatory therapies in PD prevention or treatment. There is a clear need for additional research to clarify the role of immunity and inflammation in this chronic, neurodegenerative disease.

18 Review The role of electroconvulsive and neuromodulation therapies in the treatment of geriatric depression. 2013

Riva-Posse, Patricio / Hermida, Adriana P / McDonald, William M. ·Department of Psychiatry and Behavioral Sciences, Emory University, 101 Woodruff Cir NE, Suite 4000, Atlanta, GA 30322, USA. ·Psychiatr Clin North Am · Pubmed #24229660.

ABSTRACT: Geriatric depression is associated with increased mortality because of suicide and decreases in functional and physical health. Many elders' depression is resistant to psychotherapy and medication and can become chronic. Electroconvulsive therapy (ECT) is increasingly used in the treatment of medication-resistant or life-threatening geriatric depression. Neuromodulation therapies (subconvulsive, focal, or subconvulsive and focal) are alternatives for the management of treatment-resistant depression in the elderly. Therapies that combine both strategies could be safer but may not be as effective as ECT. This review covers the evidence on the safety and efficacy of ECT and the neuromodulation therapies in geriatric depression.

19 Review Differential striatal spine pathology in Parkinson's disease and cocaine addiction: a key role of dopamine? 2013

Villalba, R M / Smith, Y. ·Yerkes National Primate Research Center, Emory University, 954, Gatewood Road NE, Atlanta, GA 30329, USA; UDALL Center of Excellence for Parkinson's Disease, Emory University, 954, Gatewood Road NE, Atlanta, GA 30329, USA. Electronic address: rvillal@emory.edu. ·Neuroscience · Pubmed #23867772.

ABSTRACT: In the striatum, the dendritic tree of the two main populations of projection neurons, called "medium spiny neurons (MSNs)", are covered with spines that receive glutamatergic inputs from the cerebral cortex and thalamus. In Parkinson's disease (PD), striatal MSNs undergo an important loss of dendritic spines, whereas aberrant overgrowth of striatal spines occurs following chronic cocaine exposure. This review examines the possibility that opposite dopamine dysregulation is one of the key factors that underlies these structural changes. In PD, nigrostriatal dopamine degeneration results in a significant loss of dendritic spines in the dorsal striatum, while rodents chronically exposed to cocaine and other psychostimulants, display an increase in the density of "thin and immature" spines in the nucleus accumbens (NAc). In rodent models of PD, there is evidence that D2 dopamine receptor-containing MSNs are preferentially affected, while D1-positive cells are the main targets of increased spine density in models of addiction. However, such specificity remains to be established in primates. Although the link between the extent of striatal spine changes and the behavioral deficits associated with these disorders remains controversial, there is unequivocal evidence that glutamatergic synaptic transmission is significantly altered in both diseased conditions. Recent studies have suggested that opposite calcium-mediated regulation of the transcription factor myocyte enhancer factor 2 (MEF2) function induces these structural defects. In conclusion, there is strong evidence that dopamine is a major, but not the sole, regulator of striatal spine pathology in PD and addiction to psychostimulants. Further studies of the role of glutamate and other genes associated with spine plasticity in mediating these effects are warranted.

20 Review Vesicular integrity in Parkinson's disease. 2013

Alter, Shawn P / Lenzi, Gina M / Bernstein, Alison I / Miller, Gary W. ·Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. ·Curr Neurol Neurosci Rep · Pubmed #23690026.

ABSTRACT: The defining motor characteristics of Parkinson's disease (PD) are mediated by the neurotransmitter dopamine (DA). Dopamine molecules spend most of their lifespan stored in intracellular vesicles awaiting release and very little time in the extracellular space or the cytosol. Without proper packaging of transmitter and trafficking of vesicles to the active zone, dopamine neurotransmission cannot occur. In the cytosol, dopamine is readily oxidized; excessive cytosolic dopamine oxidation may be pathogenic to nigral neurons in PD. Thus, factors that disrupt vesicular function may impair signaling and increase the vulnerability of dopamine neurons. This review outlines the many mechanisms by which disruption of vesicular function may contribute to the pathogenesis of PD. From direct inhibition of dopamine transport into vesicles by pharmacological or toxicological agents to alterations in vesicle trafficking by PD-related gene products, variations in the proper compartmentalization of dopamine can wreak havoc on a functional dopamine pathway. Findings from patient populations, imaging studies, transgenic models, and mechanistic studies will be presented to document the relationship between impaired vesicular function and vulnerability of the nigrostriatal dopamine system. Given the deleterious effects of impaired vesicular function, strategies aimed at enhancing vesicular function may be beneficial in the treatment of PD.

21 Review Corruption and spread of pathogenic proteins in neurodegenerative diseases. 2012

Walker, Lary C / LeVine, Harry. ·Yerkes National Primate Research Center and Department of Neurology, Emory University, Atlanta, Georgia 30329, USA. lary.walker@emory.edu ·J Biol Chem · Pubmed #22879600.

ABSTRACT: With advancing age, the brain becomes increasingly susceptible to neurodegenerative diseases, most of which are characterized by the misfolding and errant aggregation of certain proteins. The induction of aggregation involves a crystallization-like seeding mechanism by which a specific protein is structurally corrupted by its misfolded conformer. The latest research indicates that, once formed, proteopathic seeds can spread from one locale to another via cellular uptake, transport, and release. Impeding this process could represent a unified therapeutic strategy for slowing the progression of a wide range of currently intractable disorders.

22 Review Neuroinflammation and non-motor symptoms: the dark passenger of Parkinson's disease? 2012

Barnum, Christopher J / Tansey, Malú G. ·Department of Physiology, School of Medicine at Emory University, 615 Michael Street, Atlanta, GA 30324, USA. ·Curr Neurol Neurosci Rep · Pubmed #22580742.

ABSTRACT: Generally speaking, inflammation as a key piece to the Parkinson's disease (PD) puzzle is a relatively new concept. Acceptance of this concept has gained ground as studies by various researchers have demonstrated the potential of mitigating nigral cell death by curtailing inflammation in animal models of PD. We propose that the significance of inflammation in PD pathology may extend beyond the nigrostriatal region. In the current review, we present an argument for this based on the Braak staging and discuss how inflammation might contribute to the development of non-motor PD symptoms.

23 Review Industrial toxicants and Parkinson's disease. 2012

Caudle, W Michael / Guillot, Thomas S / Lazo, Carlos R / Miller, Gary W. ·Department of Environmental Health, Rollins School of Public Health, Center for Neurodegenerative Disease, Emory University, Atlanta, GA 30322, United States. William.m.caudle@emory.edu ·Neurotoxicology · Pubmed #22309908.

ABSTRACT: The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson's disease (PD) and other forms of parkinsonism. While pesticides have repeatedly been identified as risk factors for PD, these compounds represent only a subset of environmental toxicants that we are exposed to on a regular basis. Thus, non-pesticide contaminants, such as metals, solvents, and other organohalogen compounds have also been implicated in the clinical and pathological manifestations of these movement disorders and it is these non-pesticide compounds that are the subject of this review. As toxic exposures to these classes of compounds can result in a spectrum of PD or PD-related disorders, it is imperative to appreciate shared clinico-pathological characteristics or mechanisms of action of these compounds in order to further delineate the resultant disorders as well as identify improved preventive strategies or therapeutic interventions.

24 Review Parkinson's disease therapeutics: new developments and challenges since the introduction of levodopa. 2012

Smith, Yoland / Wichmann, Thomas / Factor, Stewart A / DeLong, Mahlon R. ·Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA. ysmit01@emory.edu ·Neuropsychopharmacology · Pubmed #21956442.

ABSTRACT: The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

25 Review Current status and future directions of gene expression profiling in Parkinson's disease. 2012

Greene, James G. ·Department of Neurology and the Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. jggreen@emory.edu ·Neurobiol Dis · Pubmed #21056669.

ABSTRACT: Parkinson's disease (PD) is a common age-associated neurodegenerative disorder. Motor symptoms are the cardinal component of PD, but non-motor symptoms, such as dementia, depression, and autonomic dysfunction are being increasingly recognized. Motor symptoms are primarily caused by selective degeneration of substantia nigra dopamine (SNDA) neurons in the midbrain; non-motor symptoms may be referable to well-described pathology at multiple levels of the neuraxis. Development of symptomatic and disease-modifying therapies is dependent on an accurate and comprehensive understanding of the pathogenesis and pathophysiology of PD. Gene expression profiling has been recently employed to assess function on a broad level in the hopes of gaining greater knowledge concerning how individual mechanisms of disease fit together as a whole and to generate novel hypotheses concerning PD pathogenesis, diagnosis, and progression. So far, the majority of studies have been performed on postmortem brain samples from PD patients, but more recently, studies have targeted enriched populations of dopamine neurons and have begun to explore extra-nigral neurons and even peripheral tissues. This review will provide a brief synopsis of gene expression profiling in parkinsonism and its pitfalls to date and propose several potential future directions and uses for the technique. It will focus on the use of microarray experiments to stimulate hypotheses concerning mechanisms of neurodegeneration in PD, since the majority of studies thus far have addressed that complicated issue.

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